Reductive activation of nitroaromatics and enzyme inhibition: misonidazole and xanthine oxidase

Reductive activation of misonidazole and misondiazole acetate, a simple derivative, in the presence of xanthine oxidase causes inactivation of the enzyme. The inactivation is not accompanied by binding of the misonidazole to the enzyme. The nitroreductase activity of xanthine oxidase is inhibited as measured by the reduction of 3,5-dinitrobenzonitrile (DNBN). Cysteine does not appear to protect against the enzyme inactivation by misonidazole but, by itself, cysteine has a strong stimulating effect on the reduction of DNBN. The possible significance of these reactions to the toxicity of misonidazole are discussed.